Summary

Streptomycetes have high biotechnological relevance as producers of diverse metabolites widely used in medical and agricultural applications. The biosynthesis of these metabolites is controlled by signalling molecules, γ-butyrolactones, that act as bacterial hormones. In Streptomyces coelicolor, a group of signalling molecules called SCBs (S. coelicolorbutanolides) regulates production of the pigmented antibiotics coelicolor polyketide (CPK), actinorhodin and undecylprodigiosin. The γ-butyrolactone synthase ScbA is responsible for the biosynthesis of SCBs. Here we show the results of a genome-wide transcriptome analysis of a scbA deletion mutant prior to and during the transition to antibiotic production. We report a strong perturbation in the expression of three pigmented antibiotic clusters in the mutant throughout the growth curve, thus providing a molecular explanation for the antibiotic phenotype observed previously. Our study also revealed, for the first time, that the secondary metabolite cluster responsible for synthesis of the siderophore desferrioxamine is under the control of SCB signalling. Moreover, expression of the genes encoding enzymes for primary metabolism pathways, which supply antibiotic precursors and genes for morphological differentiation, was found shifted earlier in time in the mutant. In conclusion, our time series analysis demonstrates new details of the regulatory effects of the γ-butyrolactone system in Streptomyces.

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Publication History

Issue online: 22 February 2011

Version of record online: 8 December 2010

Received 23 June, 2010; accepted 12 October, 2010.

Supporting Information

Fig. S1. Expression profiles of the butanolide cluster. Expression profiles of scbA (SCO6266) (values from qRT-PCR analysis), scbR (SCO6265) (values from qRT-PCR analysis) and scbC (SCO6267) (values from microarray analysis) are plotted for M145 (dark line) and the ΔscbA mutant (light line). The expression fold change for scbA and scbR is compared with the value in M145 at TP1, which is set as 1. Standard deviation for scbA and scbR qRT-PCR analysis at each time point is denoted in a thin light line.

Table S1. Differentially expressed genes from TP1.

Table S2. Primers used for qRT-PCR.

Table S3. Expression data. Expression values of individual genes in the clusters shown in Figs 3, 5, 6 and 7. The columns indicate the SCO number, the gene name (if available) and the normalized expression value from the microarray analysis at each time point in the wild-type M145 and the mutant M751.

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